The major objective of this proposal is to develop rapid, specific, extremely sensitive methods for the detection and analysis of nucleic acids by nucleic acid hybridization. This will involve a major effort to develop and refine two recently discovered rapid nucleic acid hybridization methods for use in DNA:DNA, DNA:RNA and RNA:RNA reactions. These methods will greatly increase the potential sensitivity of detection of nucleic acids by hybridization. Other efforts will also result in increased detection sensitivity. These include studies to increase the specific radioactivity of nucleic acid probes, to decrease the nonspecific backgrounds due to the method of measuring hybridization and work to increase the stability of nucleic acids under the conditions used for hybridization. A second objective is to test these nucleic acid hybridization methods by utilizing them to detect the presence of specific viruses in normal and diseased central nervous sytem (CNS) tissue. Many diseases of the CNS are disorders of unknown etiology. In the past decade several of these diseases have been shown to be associated with specific viruses. It is of interest to examine other CNS diseases for the presence of specific viruses. Nucleic acid hybridization provides a highly specific, extremely sensitive tool to do this.